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Lifestyle Interventions: Lifestyle Interventions:

Dietary Therapy, Physical Activity, Dietary Therapy, Physical Activity,

Weight ControlWeight Control

Neil J. Stone, M.D.Neil J. Stone, M.D.



0% 20% 40% 60% 80%

20102010 NowNow

Primary Prevention: Primary Prevention: Status and Goals Status and Goals in 2010in 2010

NCEP. Adult Treatment Panel III Report. 2001.

Moderate Moderate physical activityphysical activity

Vegetable intake Vegetable intake of >3 servingsof >3 servings

Saturated fat Saturated fat <10% of calories<10% of calories



0% 20% 40% 60% 80%

Primary Prevention: Primary Prevention: Status and Goals Status and Goals in 2010in 2010

Fruit >2 servings/dFruit >2 servings/d

Smoking cessationSmoking cessation

Healthy weightHealthy weight

20102010 NowNow

NCEP. Adult Treatment Panel III Report. 2001.



-60%-40%-20%0%

Primary Prevention: Primary Prevention: Crucial Opportunity to Crucial Opportunity to Reduce the Burden of CHDReduce the Burden of CHD

Law MR et al. BMJ 1994;308:367-372.

Age 70Age 70

Reduction in risk in men with 10% reductionReduction in risk in men with 10% reductionin total cholesterol (10 cohort studies)in total cholesterol (10 cohort studies)

Age 50Age 50

Age 40Age 40



Primary Prevention: Primary Prevention: Adverse Life Habit Adverse Life Habit ChangesChanges

Atherogenic diet

Sedentary lifestyle

Obesity

Expert Panel. JAMA 2001;285:2486-2497.



Primary Prevention—Rx: Primary Prevention—Rx: Therapeutic Therapeutic Lifestyle Changes (TLC)Lifestyle Changes (TLC)

Therapeutic diet to lower LDL-C

Physically active on a daily basis

Weight control




Primary Prevention—Rx: Primary Prevention—Rx: TLC Measures to TLC Measures to Lower LDL-CLower LDL-C

Saturated fats (<7% total calories) and cholesterol (<200 mg/d)

Also therapeutic options:

— Plant stanols/sterols (2 g/d)

— Increased viscous fiber (10–25 g/d)




Total Fat...Why a range?Total Fat...Why a range?

Primary emphasis is to reduce saturated fats Total fat should range 25–30% for most cases

Those with metabolic syndrome Avoid very high fat intakes Avoid very low fat intake (low HDL-C, high TG) Total fat intake can range from 30–35% if extra fat is

unsaturated May reduce some lipid and nonlipid risk factors Clinical judgment required.



Therapeutic Lifestyle Changes:Therapeutic Lifestyle Changes:Nutrient Composition of TLC DietNutrient Composition of TLC Diet

NutrientNutrient Recommended IntakeRecommended Intake

Saturated fat*Saturated fat* Less than 7% of total caloriesLess than 7% of total calories

Polyunsaturated fatPolyunsaturated fat Up to 10% of total caloriesUp to 10% of total calories

Monounsaturated fatMonounsaturated fat Up to 20% of total caloriesUp to 20% of total calories

Total fatTotal fat 25–35% of total calories25–35% of total calories

Carbohydrate**Carbohydrate** 50–60% of total calories50–60% of total calories

FiberFiber 20–30 grams per day20–30 grams per day

ProteinProtein Approximately 15% of total caloriesApproximately 15% of total calories

CholesterolCholesterol Less than 200 mg/dayLess than 200 mg/day

Total calories (energy)Total calories (energy) Balance energy intake and output to Balance energy intake and output to maintain expendituremaintain expenditure healthy body healthy body weight/prevent weight gainweight/prevent weight gain

* Lower * Lower transtrans fatty acids fatty acids** Emphasize complex sources** Emphasize complex sources



LDL-C Response to Step II Diet: LDL-C Response to Step II Diet: beFITbeFIT

178 Women / 231 MenDietary fat 25%; saturated fat 7.5%

LDL reduction High cholesterol only: –7.6 to 8.8%

LDL reduction Combined hyperlipidemia:–8.1%

Walden CE et al. Arterioscler Thromb Vasc Biol 1997;17:375-382.



DELTA I Dietary TrialDELTA I Dietary Trial

Subjects:Subjects: age 22 to 67 Different groups of subjects:

White, black Women: younger and

postmenopausal Men: younger, older

-20%

-10%

0%

10%

20%

30%

40%

AADAAD Low SatLow SatResults:Results: Compared to average

American diet, when saturated fat fell from 15% to 6.1%, LDL-C fell by 11%

Negative aspects:Negative aspects: HDL-C fell from 52.2 to 46.2 Lp(a) rose from 15.5 to 18.2

Ginsberg HN et al. Arterioscler Thromb Vasc Biol 1998;18:441-449.

Total Fat Sat Fats LDL



New Options to Lower LDL-CNew Options to Lower LDL-C

Avoid

Trans fatty acids*

Add

Dietary fiber

Plant sterol/stanol ester margarines


* Keep trans fatty acids low



TransTrans Fatty Acids (TFA) Fatty Acids (TFA)

TFA more densely packed than cis forms

Usual intake: only 2–3% of energy

If consumed in high amounts: LDL-C; HDL-C

Examples of TFAStick margarine, cookies, biscuits, white bread

Lichtenstein AH et al. N Engl J Med 1999;340:1933-1940

Conclusion:Conclusion: Consume products low in Consume products low in saturated and TFAsaturated and TFA



Plant Sterol/Stanol EstersPlant Sterol/Stanol Esters

Sterols are essential components of cell membranes

Cholesterol exclusively an animal sterol

We ingest almost as much plant sterols as we do dietary cholesterol

Stanols absorbed even less well

Plant sterols/stanols lower cholesterol

Interfere with micellar absorption of cholesterol

No malabsorption of fat

Law MR et al. BMJ 2000;320:861-864.



Plant Sterol/Stanol EstersPlant Sterol/Stanol Esters

If 2 g of plant sterol or stanol is added to average daily portion of margarine, it has variable effect on LDL-C by age group:

Age LDL-C reduced by:

50–59 21 mg/dl or 0.54 mmol/l

40–49 17 mg/dl or 0.43 mmol/l

30–39 13 mg/dl or 0.33 mmol/l

Law MR et al. BMJ 2000;320:861-864.



Esterification of StanolsEsterification of Stanols Plant Stanol Crystalline powder

Restricted fat solubility

Melting range 140–150oC

R C -

= O 33

5566

OO

33

5566

HOHO

1717

EsterificationEsterification

Fat-SolubleFat-SolublePlant StanolPlant Stanol



200

210

220

230

240

250Treatment with Stanol Ester MargarineTreatment with Stanol Ester Margarine

-2-2

Chole

stero

l (m

g/d

l)

Study Period (mo)Study Period (mo)22 44 88 1010

Miettinen TA et al. N Engl J Med 1995;333:1308-1312.1995 Massachusetts Medical Society. All rights reserved.

00 1212 141466

Sitostanol-ester margarineSitostanol-ester margarine



Plant Sterols/Stanols: Efficacy in Lowering Plant Sterols/Stanols: Efficacy in Lowering LDL-CLDL-C

Dose: Maximum is 2 g/d

Meta-analysis results: LDL-C lowering about 9–13%

Lowering greater in elderly Additive to statin therapy Used in various population groups

Well-tolerated

May decrease LDL-C adjusted carotenoids

Law M et al. BMJ 2000;320:861-864.Lichtenstein AH et al. Circulation 201;103:1177-1179



Dietary AdjunctsDietary Adjuncts TLC for patients with LDL-C = 160

Walden CE et al. Arterioscler Thromb Vasc Biol 1997;17:375-382.Jenkins DJ et al. Curr Opin Lipidol 2000;11:49-56.Cato N. Stanol meta-analysis. Personal communication, 2000.

Dietary ComponentDietary Component LDL-C LDL-C (mg/dL) (mg/dL)

Low saturated fat/dietary Low saturated fat/dietary cholesterolcholesterol ––1212

Viscous fiber (10–25 g/d)Viscous fiber (10–25 g/d) – –88

Plant stanols/sterols (2 g/d)Plant stanols/sterols (2 g/d) ––1616

TotalTotal – –36 mg/dl36 mg/dl



The Spectrum of CHD RiskThe Spectrum of CHD Risk


““More higher risk patients brought into the algorithm”More higher risk patients brought into the algorithm”

MetabolicMetabolicSyndromeSyndrome

ElevatedElevatedLDL-CLDL-C

GlucoseGlucose 110–125110–125 AbdominalAbdominal Obesity Obesity HDL-CHDL-C BPBP TG TG 150150



The Metabolic SyndromeThe Metabolic Syndrome Constellation of major risk

factors, life-habit risk factors and emerging risk factors

Over-represented among populations with CHD

Clue is distinctive body-type with increased abdominal circumference (although some leaner men and women with abdominal obesity without increased waist)



Metabolic Syndrome as a Secondary Goal Metabolic Syndrome as a Secondary Goal after LDL-Cafter LDL-C


Risk Factor (Risk Factor (3)3) Defining LevelDefining Level

Abdominal obesityAbdominal obesity Waist circumferenceWaist circumference**

TriglyceridesTriglycerides 150 mg/dl150 mg/dl

HDL-CHDL-C<40 mg/dl in men; <40 mg/dl in men; <50 mg/dl in women<50 mg/dl in women

Blood pressureBlood pressure 130/130/85 mm Hg85 mm Hg

Fasting glucoseFasting glucose 110 mg/dl110 mg/dl

* Men: >40 in (102 cm); women >35 in (88 cm)* Men: >40 in (102 cm); women >35 in (88 cm)



Metabolic Syndrome as a Secondary Goal Metabolic Syndrome as a Secondary Goal after LDL-Cafter LDL-C


Risk FactorRisk Factor Defining LevelDefining Level

Abdominal obesityAbdominal obesity> 40 waist circ. in men> 40 waist circ. in men> 35 waist circ. in women> 35 waist circ. in women

HDL-CHDL-C< 40 mg/dl in men< 40 mg/dl in men< 50 mg/dl in women< 50 mg/dl in women

Circ. = circumference measured at level of the Circ. = circumference measured at level of the iliac spine iliac spine



Clustering of Risk Factors Incorporated Clustering of Risk Factors Incorporated into the Metabolic Syndromeinto the Metabolic Syndrome

Includes risk factors not routinely measured

Insulin resistance

Small dense LDL

Endothelial dysfunction

Abnormal sympathetic nervous activity

Prothrombotic markers—PAI-1, fibrinogen

Proinflammatory markers such as CRP



Does Treating the Metabolic Syndrome Does Treating the Metabolic Syndrome Make a Difference? Make a Difference? Finnish Diabetes Finnish Diabetes Prevention StudyPrevention Study

Design522 middle-aged overweight (BMI 31)172 men and 350 womenMean duration 3.2 years

Intervention Group: Individualized counselingReducing weight, total intake of fat and

saturated fat Increasing uptake of fiber, physical activity

Tuomilehto J et al. N Engl J Med 2001;344:1343-1350.



Treating the Metabolic SyndromeTreating the Metabolic Syndrome

Goals Goals

InterventionIntervention ControlsControls

P valueP value% of subjects% of subjects

Wt reduction >5%Wt reduction >5% 4343 1313 0.0010.001

Fat intake < 30% Fat intake < 30% energyenergy

4747 2626 0.0010.001

Sat fat Sat fat <10% energy<10% energy

2626 1111 0.0010.001

Fiber Fiber >15 g/1000 kcal>15 g/1000 kcal

2525 1212 0.0010.001

Exercise > 4 hr/wkExercise > 4 hr/wk 8686 7171 0.0010.001




Benefit of Treating the Metabolic SyndromeBenefit of Treating the Metabolic Syndrome


0%

5%

10%

15%

20%

25%

InterventionIntervention ControlControl

After 4 After 4

years — years —

risk of risk of

diabetes diabetes

reduced reduced

by by 58%58%

11%11%

23%23%

(6–15 (6–15 CI)CI)

(17–29 (17–29 CI)CI)

% with Diabetes% with Diabetes



Goals of Weight LossGoals of Weight Loss1. Reduce body weight in the short term

2. Maintain a lower body weight for the long term

3. Prevent further weight gain — minimum goal

Obesity Education Initiative. Clinical Guidelines on the Identification, Evaluation and Treatment of Overweight and Obesity in Adults: the Evidence Report. Bethesda, Md.: NIH, 1998



Further Goals of Weight LossFurther Goals of Weight Loss1. Rate of weight loss

10% reduction in body weight in 6 months of therapy

Rate is 1–2 lbs per week



Goals of Physical ActivityGoals of Physical ActivityPeople of all ages, male and female benefit People of all ages, male and female benefit

from physical activityfrom physical activity

1. Include a moderate amount of physical activity on most, if not all days of the week

2. Additional health benefits can be derived from greater amounts of activity

3. Emphasis is on amount not intensity

U.S. Dept. of Health and Human Services. Physical Activity and Health:A Report of the Surgeon General. Atlanta, Ga: Centers for Disease Control and Prevention, 1996.



Suggestions on ActivitySuggestions on Activity1. Scheduled physical activity

a. Walking, treadmill, jogging, walking dog

b. Swimming, biking, volleyball

2. Lifestyle physical activity

a. Walk more stairs at work, walking for errands, parking farther away in parking lots

b. Housework, gardening

U.S. Dept. of Health and Human Services. Physical Activity and Health:A Report of the Surgeon General. Atlanta, Ga: Centers for Disease Control and Prevention, 1996.



Metabolic Benefits of Weight LossMetabolic Benefits of Weight Loss Reverse changes of insulin resistance and

metabolic syndrome

Raise HDL-C (can see increase of 1.6 mg/dl from a 10-lb weight loss)

Dattilo AM et al. Am J Clin Nutr 1992;56:320-328.



-8

-7

-6

-5

-4

-3

-2

-1

0

Metabolic Response to 10-lb Weight Loss: Metabolic Response to 10-lb Weight Loss: Framingham DataFramingham Data

Higgins M et al. Acta Med Scand Suppl 1988;723:23-36.

CholesterolCholesterol

Small Small

changes changes

can add up can add up

to to

significant significant

changes in changes in

long-term long-term

riskrisk Syst BPSyst BP GlucoseGlucose

mg/dlmg/dl mm Hgmm Hg mg/dlmg/dl

MenMen

WomenWomen



Dietary Options — Benefit Independent of Dietary Options — Benefit Independent of LDL-C LoweringLDL-C Lowering

AvoidAvoid Megavitamins (adverse effects shown for

supplements of beta-carotene, no convincing clinical trial benefit for vitamin E supplementation)

AddAdd Fish

Plant sources of omega-3 fatty acids

Fruits and vegetables



Clinical Trial Data Showing Lack of Benefit Clinical Trial Data Showing Lack of Benefit of Megavitaminsof Megavitamins

Beta Carotene No proof of benefit in 3 trials One stopped prematurely (CARET)

Vitamin E No proof of benefit in 2 large trials

HOPE Trial – Natural vitamin EGISSI Prevention – Synthetic vitamin E

Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study Group. N Engl J Med 1994;330:1029-1035. Hennekens CH et al. N Engl J Med1996;334:1145-1149. Omenn GS et al. N Engl J Med 1996;334:1150-1155. HOPE Study Investigators. N Engl J Med 2000;342:154-160. GISSI-Prevenzione Investigators. Lancet 1999;354:447-455.



Clinical Trial Data Showing Significant Clinical Trial Data Showing Significant Effect of DietEffect of Diet

Omega-3 Fatty Acids

DART: 29% reduction in death

GISSI: Significant reduction of one of two combined endpoints

“Mediterranean Diet”

Lyon Trial: Multiple differences in diet; diet was low in animal, dairy fat, high in plant-based omega-3 fatty acids, fiber

Burr ML et al. Lancet 1989;2:757-761. GISSI-Prevenzione Investigators.Lancet 1999;354:447-455. de Longeril M et al. Circulation 1999;99:779-785.



Burr ML et al. Lancet 1989;2:757-761. GISSI-Prevenzione Investigators.Lancet 1999;354:447-455.

Trials of n-3 Fatty Acids in MI Survivors: Trials of n-3 Fatty Acids in MI Survivors: Significant Effect on DeathsSignificant Effect on Deaths

0.0%1.0%2.0%3.0%4.0%5.0%6.0%7.0%8.0%

DARTDART GISSIGISSI3,482 patients3,482 patients 11,324 patients11,324 patients

Expt DeathsExpt Deaths

Control DeathsControl Deaths



70

80

90

100

Lyon Diet Heart Study: Lyon Diet Heart Study: Cumulative Survival Cumulative Survival without Cardiac Death and Nonfatal MIwithout Cardiac Death and Nonfatal MI

de Lorgeril M et al. Circulation 1999;99:779-785.1999 Lippincott Williams & Wilkins. www.lww.com

11

% W

ithout

Event

Canola oil– Canola oil– based based margarine, margarine, fiber, low fiber, low cholesterol, cholesterol, low saturated low saturated fat, fruits, fat, fruits, vegetablesvegetables

ExperimentalExperimental

ControlControl

P = 0.0001P = 0.0001

YearYear22 33 44 55



Comparison of the DietsComparison of the DietsItemItem ExperimentalExperimental ControlControl

Total caloriesTotal calories 19471947 2088*2088*

Total fatTotal fat 30.4%30.4% 33.6%*33.6%*

Saturated fatSaturated fat 8%8% 11.7%11.7%

Dietary cholesterolDietary cholesterol 203 mg/dl203 mg/dl 312 mg/dl*312 mg/dl*

AlcoholAlcohol SameSame SameSame

Olive oilOlive oil NoneNone NoneNone

MUFA n-9MUFA n-9 Increased*Increased*

PUFAPUFA Increased*Increased*

n-3/n-6 fatty acidsn-3/n-6 fatty acids Increased*Increased*

FiberFiber 18.618.6

de Lorgeril M et al. Circulation 1999;99:779-785.*Significantly different*Significantly different



How to Implement Primary Prevention with How to Implement Primary Prevention with TLCTLC

Stepwise approach

Resources

Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults (download from web for palm-based material)

Surgeon General’s Report on Physical Activity



Implementing Primary Prevention Implementing Primary Prevention with TLC?with TLC?

Emphasize reduction in saturated fat and cholesterol

Reduce animal/high fat dairy

Get lower fat food if eats out

Regular physical activity

Visit 1Visit 1





Evaluate LDL-C response

Intensify LDL-C lowering with dietary adjuncts

Plant stanols/sterols

Increased fiber intake

Visit 2Visit 2




Implementing Primary Prevention Implementing Primary Prevention with TLCwith TLC

At all stages of dietary therapy, physicians are encouraged to refer patients for:

Medical nutrition therapy

Registered dietitians/other qualified nutritionists





Evaluate LDL-C response

Initiate therapy for metabolic syndrome

Intensify weight management

Physical activity

Consider drug Rx if LDL-C goal not achieved

Visit 3Visit 3




Primary Prevention with TLCPrimary Prevention with TLC Therapeutic Lifestyle Changes can lower LDL-C so

medication not required or increase not needed

Can treat metabolic syndrome

Lowers TG

Raises HDL-C

Reduces risk of diabetes

Provides overall healthful lifestyle


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